Schizophrenia is one of the world's major unsolved public health problems. It is a relatively common, chronic, debilitating disease of variable expression. Little is known about the causes of schizophrenia but there is convincing evidence that genetic factors play some role in the etiology of schizophrenia. However, the mechanism is not known. Most investigators believe schizophrenia is etiologically heterogeneous. The long term objective of this study is to identify the genes associated with susceptibility to this complex disease. This will be achieved through molecular genetic approaches. Linkage analysis and linkage disequilibrium studies using highly polymorphic microsatellite markers in a unique genetically homogeneous community (Ashkenazi Jews) will be conducted. The specific aims of the proposal are as follows: 1) to recruit and evaluate a sample of 150 Ashkenazi Jewish patients who are diagnosed as having either schizophrenia or schizoaffective disorder (depressed type) and whose parents are willing to participate (trio panel). It is anticipated that 50 such trios will be identified prior to the beginning of this study, from other sources of funding so that the total trio sample will be comprised of 200 Ashkenazi Jewish patients and their parents. DNA will be isolated and lymphocytes will be isolated, frozen and stored; 2) to recruit and evaluate an independent sample of 100 Ashkenazi Jewish families with affected siblings and at least one parent willing to participate. Virus transformed lymphoblastoid cell lines from the affected siblings and their parents in the 100 sib-pair families will be obtained as well as DNA from direct extraction; 3) to genotype highly polymorphic microsatellite markers in regions of interest previously identified in other populations in both the trio sample and the sib-pair sample, as well as to complete genome-wide scans in both the trio sample and the sib-pair sample to detect new susceptibility loci; 4) to follow-up families to maintain current affected status; and 5) to make this unique clinical resource available to other investigators pursuing this goal.